The laboratory of Dr. Peter S. McPherson, James McGill Professor, uses biochemical, molecular, structural and cellular approaches to identify and functionally characterize proteins that function in the formation of clathrin-coated vesicles (CCVs). CCVs are the major vehicles for endocytic uptake of multiple protein and lipid cargo, including nutrient and signaling receptors. Moreover, neurons depend on CCVs for the reformation of synaptic vesicles in the presynaptic nerve terminal following neurotransmitter release. In addition to understanding the basic mechanisms of CCV formation and endocytic function, Dr. McPherson's studies demonstrate how endocytosis is linked to cell processes such as signaling and regulation of the actin cytoskeleton. Further developments of these links represent an ongoing focus of his research.

Dr. McPherson's laboratory has previously used subcellular proteomics (subcellular fractionation coupled to high throughput mass spectrometry) to identify the full complement of proteins that define CCVs from adult brain, developing brain and non-neuronal tissues. A significant number of the proteins identified were uncharacterized open-reading frames. Dr. McPherson's laboratory has characterized the function of a number of these novel proteins, although a significant number remain unstudied. One recently identified protein contains a module called a DENN domain. Dr. McPherson and his colleagues have demonstrated that the DENN domain functions enzymatically as a guanine-nucleotide exchange factor for the small GTPase Rab35. There are 16 DENN domain proteins in the human genome. An important area of study involves the relationship of these proteins to the ~60 Rabs that function in membrane traffic.

A number of proteins identified in the McPherson laboratory have been linked to neurological diseases, including schizophrenia, Huntington's Disease, hereditary spastic paraplegias (ALS-like), and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Indeed, dysregulation of membrane trafficking is emerging as a central theme in neurodegenerative diseases. Understanding the cell biological basis of neurological disease is a new focus of the laboratory.

See Publications

E-mail: Peter McPherson
Web Site: McPherson Lab